Kidney survival analysis was performed for 64 patients with focal segmental sclerosis to ascertain whether the degree of proteinuria and other factors determined at the time of renal biopsy might be associated with progression to end-stage renal failure. On the basis of urinary excretion of protein, which was measured in 63 of the 64 patients, three groups of patients were identified: 15 patients (group A) had asymptomatic proteinuria (less than 3.5 g/24 h), 38 patients (group B) had nephrotic proteinuria (3.5 to 14 g/24 h), and 10 patients (group C) had massive proteinuria (more than 14 g/24 h). Kidney survival curves showed that the median time from biopsy to end-stage renal failure was more than 11, 7, and 3 years for groups A, B, and C, respectively. Thus, patients with massive proteinuria had an accelerated course to renal failure as compared with other nephrotic patients who had a lesser degree of proteinuria (P = 0.014) and patients who had asymptomatic proteinuria (P less than 0.001). Higher initial serum creatinine levels and severe tubulointerstitial damage were associated with a shorter time to end-stage renal failure. Age at onset and at biopsy, systolic and diastolic blood pressure, serum albumin and cholesterol, percentage of sclerotic glomeruli, mesangial proliferation, hyalinosis, vascular sclerosis, and initial response to prednisone were not associated with the time to end-stage renal failure when each of these variables was considered separately.